An understanding of pathologic body fluid retention and hypertension requires knowledge of renal regulation of salt excretion. Intra-renal transport processes play key roles in this regulation. The objective of the proposed research is to quantitatively analyze how these processes affect salt excretion. Specifically, we shall test hypotheses involving nephron heterogeneity, renal blood flow distribution, membrane transport mechanisms, natriuretic hormones, and medullary concentration gradients in determining the extent of naturiuresis under various physiological conditions. For this purpose, we shall use mathematical modeling and computer simulation. The model distinguishes and accounts for transport processes in all tubule segments and vasculature in the cortex and medulla. Values of anatomical and membrane transport parameters obtained from the literature, e.g., isolated tubule experiments, will be used in computer simulations to test the consistency of a variety of hypotheses. Also, from our model and simulation studies, critical experiments needed to discriminate among regulatory mechanisms will be identified.